霉酚酸酯对血管内皮细胞白细胞介素-6产生的影响

Mycophenolate mofetil inhibits interleukin-6 secretion in human endothelial cells

目的 :观察霉酚酸酯 (MMF)对炎症因子刺激下人脐静脉内皮细胞白细胞介素 6 (IL 6 )分泌的影响。 方法 :以TNFα(10 μg/L)刺激人脐静脉内皮细胞 ,同时加用霉酚酸 (MPA ,10或 5 0 μmol/L)和鸟嘌呤核苷 (10 0μmol/L)共同孵育 ,采用ELISA法检测细胞上清IL 6的分泌量。 结果 :TNFα刺激内皮细胞 2 4h后 ,内皮细胞分泌的IL 6明显增加 [(114 85± 5 2 1 3)vs (12 91 7± 10 8 6 )ng/ (L·10 6cell) ,P <0 0 1]。MPA可以抑制TNFα诱导的内皮细胞IL 6的分泌 [(485 7 7± 2 34 5 )vs (12 818 7± 72 5 6 )ng/ (L·10 6cell) ,P <0 0 1],且随着MPA剂量的增加 ,抑制作用加强 ;添加外源性的鸟嘌呤核苷不能逆转MPA抑制内皮细胞分泌IL 6的作用 [(42 5 4 0± 6 72 8)vs (374 7 3±82 1 8)ng/ (L·10 6Cell],P >0 0 5 )。 结论 :MMF可以抑制炎症因子诱导的内皮细胞IL 6的分泌 ,且此作用与抑制嘌呤代谢无关。

Objective:To investigate the effect of mycophenolate mofetil (MMF) on interleukin-6 (IL-6) secretion in human endothelial cells.A human umbilical vein endothelial cell line (HUVEC) from ATCC was used, and the effect of mycophenolic acid (MPA), active metabolite of MMF, was observed in the study. HUVEC were treated with TNFα or TNFα+MPA or TNFα+MPA+guanosine for 24 hours. The secretion of IL-6 was measured with enzyme linked immunosorbent assay (ELISA).TNFα(10 ng/L) significantly increased IL-6 secretion in HUVEC [ 11 485 ±521 3 vs 1 291 7 ±108 6 ng/(L·10 6 cell), P <0.01], and this effect was attenuated by MPA (10 or 50 μmol/L) in a dose-dependent manner. Addition of guanosine had no effect on IL-6 secretion inhibited by MPA [ 4 254 0 ±672 8 vs 3 747 3 ±821.8 ng/(L·10 6 cell), P >0.05], indicating that inhibition of purine synthesis is not responsible for reduced IL-6 secretion. MMF inhibits IL-6 secretion induced by TNFα in human endothelial cells, and this effect may be associated with MMF's therapeutic effects in vasculitis and inflammatory diseases.